Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline

Abstract

Increasing evidence has challenged the traditional view about the immune privilege of the brain, but the precise roles of immune cells in regulating brain physiology and function remain poorly understood. Here, we report that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus of aged brains. ILC2 in the aged brain are long-lived, are relatively resistant to cellular senescence and exhaustion, and are capable of switching between cell cycle dormancy and proliferation. They are functionally quiescent at homeostasis but can be activated by IL-33 to produce large amounts of type 2 cytokines and other effector molecules in vitro and in vivo. Intracerebroventricular transfer of activated ILC2 revitalized the aged brain and enhanced the cognitive function of aged mice. Administration of IL-5, a major ILC2 product, was sufficient to repress aging-associated neuroinflammation and alleviate aging-associated cognitive decline. Targeting ILC2 in the aged brain may provide new avenues to combat aging-associated neurodegenerative disorders.

Glycyrrhizic Acid Improves Cognitive Levels of Aging Mice by Regulating T/B Cell Proliferation

“…The brain is particularly susceptible to the effects of aging, and aging-associated inflammation is a major risk factor for a variety of neurocognitive and neurodegenerative diseases ( Fung et al, 2020 ). There are abnormal neural stem cells, neurons, and microbes in the brain, and their clearance by immune cells can preserve cognitive function ( Bussian et al, 2018 ).…”

Dysregulation of adipose ILC2 underlies thermogenic failure in aging

“…All mice were on the C57BL/6J genetic background. Adult (8-12 weeks old) and old (18)(19)(20)(21)(22)(23)(24) months old) mice were obtained from Jackson Labs or the National Institute on Aging (NIA) Aged Rodent Colony, and comparisons were made between groups of mice from the same vendor. Red5 mice were purchased from Jackson Labs (stock #030926) and were originally generated and described by Nussbaum et al (44).…”

“…We were especially intrigued by the loss of ILC2 in aged visceral adipose tissue because of their important role in promoting metabolic health and cold tolerance (17)(18)(19), both of which are impaired during aging. ILC2 exhibit strong tissue specificity (20) and are uniquely regulated in different tissues during the aging process (21)(22)(23), indicating that specific regulatory mechanisms might be responsible for their depletion in aged adipose tissue.…”

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

“…Tissueresident ILC2 are implicated in tissue repair, tissue remodeling, and metabolic homeostasis [94]. Recently, it was shown in the choroid plexus of the brain that ILC2 in the aged brain are long-lived and capable of reversibly switching between cell cycle dormancy and proliferation [95]. They are relatively resistant to cellular senescence and exhaustion under replication stress, leading to enhanced self-renewal capability.…”